Monoclonal antibodies reactive with various human tumor cells have been prepared from murine hybridomas according to standard techniques. Phase I trials of antitumor monoclonal antibodies initiated by the Clinical Investigations Section include studies of anti-T cell monoclonal antibodies in patients with chronic lymphocytic leukemia (CLL) and cutaneous T cell lymphoma (CTCL), anti-melanoma monoclonal antibody in patients with disseminated melanoma, and anti-idiotype monoclonal antibody in patients with malignant lymphoma and CLL. We have treated 12 patients with CLL and 8 patients with CTCL with the T101 monoclonal antibody. We have witnessed transient reductions in circulating leukemic cells but have not seen reductions in the size of enlarged organs or lymph nodes. Five of 8 patients with CTCL had minimal improvement in their skin lesions. Toxicity has included mild fever and minimal shortness of breath. Eight patients with metastatic melanoma have been treated with an antibody to a 250,000 m.w. melanoma associated antigen. While we have seen no reductions in the size of metastatic lesions, we have seen in vivo localization of antibody in cutaneous lesions. We have successfully developed anti-idiotype antibodies for 2 patient with B-cell lymphomas and one with CLL and expect to treat these patients in the next 3-6 months.